Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10-producing T cells and increased lamina propria plasmacytoid dendritic cells

• Published in: Clinical and experimental immunology Vol. 155; no. 3; pp. 447 - 456
• Main Authors: Mannon, P.J, Leon, F, Fuss, I.J, Walter, B.A, Begnami, M, Quezado, M, Yang, Z, Yi, C, Groden, C, Friend, J, Hornung, R.L, Brown, M, Gurprasad, S, Kelsall, B, Strober, W
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2009; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Adult; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Blood; Crohn Disease - drug therapy; Crohn Disease - immunology; Crohn's Disease; Cytokines; Cytokines - immunology; Dendritic Cells - immunology; Drug Administration Schedule; Female; FoxP3; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Granulocyte Colony-Stimulating Factor - therapeutic use; Humans; Immunohistochemistry; Immunophenotyping; Interleukin; Interleukin-10 - immunology; Laminates; Lymphocyte Activation - immunology; Male; Medical sciences; Medical services; Mucous Membrane - immunology; Original; Other diseases. Semiology; Patients; Pilot Projects; plasmacytoid dendritic cells; Recombinant Proteins; regulatory T cells; Statistics, Nonparametric; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes, Regulatory - immunology; Th1 inflammation; Therapy; Treatment Outcome; Young Adult; Dendritic cell; Cytokine; Lamina propria; Th1 lymphocyte; Biochemistry; Inflammation; Plasmacytoid dendritic cell; Inflammatory disease; regulatory T cells; Crohn disease; Granulocyte colony stimulating factor; plasmacytoid dendritic cells; Association; Treatment; Antigen presenting cell; Interleukin 10; T-Lymphocyte; Digestive diseases; Intestinal disease; cytokines; FoxP3; Th1 inflammation; Regulatory cell; Transcription factor FOXP3
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2008.03799.x

Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 μg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4⁺ memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123⁺ plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-γ production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa.